Ritter-enabled catalytic asymmetric chloroamidation of olefins

Steigerwald, Daniel C; Soltanzadeh, Bardia; Sarkar, Aritra; Morgenstern, Cecilia C; Staples, Richard J.; Borhan, Babak

doi:10.1039/d0sc05224h

Cited by 10 publications

(2 citation statements)

References 103 publications

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“…Using (DHQD) 2 PHAL as the organocatalyst, our labs have explored stereocontrolled halofunctionalizations with various alkene substrates, chlorenium sources, and nucleophiles. These reactions include chlorocyclizations of alkenoic acids, alkeneamides, , and alkene carbamates, where the nucleophilic moiety is intramolecular, as well as reactions like chloro-etherification/amidation and dichlorination where nucleophilic attack is intermolecular. ,, Nicolaou, Hennecke, and other groups have also reported the use of (DHQD) 2 PHAL-type catalysts for asymmetric halofunctionalizations. , The sheer numbers of successful applications speak to the robustness and versatility of these cinchona alkaloid catalysts in asymmetric halofunctionalization methodologies.…”

Section: Introductionmentioning

confidence: 99%

Structure–Enantioselectivity Relationship (SER) Study of Cinchona Alkaloid Chlorocyclization Catalysts

et al. 2023

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Various structural elements of the Cinchona alkaloid dimers are interrogated to establish a structure–enantioselectivity relationship (SER) in three different halocyclization reactions. SER for chlorocyclizations of a 1,1-disubstituted alkenoic acid, a 1,1-disubstituted alkeneamide, and a trans-1,2-disubstituted alkeneamide showed variable sensitivities to linker rigidity and polarity, aspects of the alkaloid structure, and the presence of two or only one alkaloid side group defining the catalyst pocket. The conformational rigidity of the linker–ether connections was probed via DFT calculations on the methoxylated models, uncovering especially high barriers to ether rotation out of plane in the arene systems that include the pyridazine ring. These linkers are also found in the catalysts with the highest enantioinduction. The diversity of the SER results suggested that the three apparently analogous test reactions may proceed by significantly different mechanisms. Based on these findings, a stripped-down analogue of (DHQD)2PYDZ, termed “(trunc)2PYDZ”, was designed, synthesized, and evaluated, showing modest but considerable asymmetric induction in the three test reactions, with the best performance on the 1,1-disubstituted alkeneamide cyclization. This first effort to map out the factors essential to effective stereocontrol and reaction promotion offers guidance for the simplified design and systematic refinement of new, selective organocatalysts.

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Section: Introductionmentioning

confidence: 99%

Structure–Enantioselectivity Relationship (SER) Study of Cinchona Alkaloid Chlorocyclization Catalysts

et al. 2023

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“…Therefore, the Ritter reaction has attracted attention from the synthetic community, and diverse synthetic strategies have been developed in the past decade. [16][17][18][19][20][21] Among them, the C-H bond oxidation strategy for producing reactive carbocation intermediates could avoid the preparation of synthetic precursors bearing an additional leaving group or a suitable C=C double bond, and thus dramatically improves the efficiency of the Ritter reaction. 5,19-Therefore, further expansion of the substrate scope to produce variously functionalized and synthetically valuable amides is highly desirable but underdeveloped.…”

Section: Introductionmentioning

confidence: 99%

Exploration of Oxidative Ritter-Type Reaction of α-Arylketones and Its Application for the Collective Total Syntheses of Erythrina Alkaloids

Chen

Tang

et al. 2022

CCS Chem

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Although the classical Ritter reaction has been widely applied to prepare sterically hindered amides since 1948, it has intrinsic problems, such as harsh reaction conditions, the multistep preparation of synthetic precursors, and the use of solvent quantities of nitrile. In particular, only a few examples of the total syntheses of natural products using the Ritter reaction as a key step have been reported to date. In this article, an oxidative Ritter-type reaction of α-arylketones was developed to efficiently construct a sterically hindered N-acyl aza-quaternary carbon moiety. The current transformation features the use of 10 equivalents of nitriles, a broad substrate scope (81 examples), a short reaction time, and mild reaction conditions; notably, both of the use of a limited amount of nitriles and the producing carbocation intermediates via the C-H bond oxidation strategy address two intractable problems of the classical Ritter reaction. Furthermore, based on an unprecedented synthetic strategy using this oxidative Ritter reaction to construct a C-5 aza-quaternary carbon center, the collective total syntheses of erythrina alkaloids, including erysotramidine, 11-α-methoxyerysotramidine, 11-β-hydroxyerysotramidine, erytharbine, the proposed 11-βmethoxyerysotramidine and 10,11-dioxoerysotramidine, and the unnatural 11-α-hydroxyerysotramidine, have been completed using a common precursor through a one-step chemical transformation.

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Oxidative Ritter‐type Chloroamidation of Alkenes Using NaCl and Oxone

et al. 2021

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We report a practical and environmentally benign method for the oxidative Ritter‐type chloroamidation of alkenes using sodium chloride and oxone as a chlorinating source and an oxidant, respectively, in acetonitrile under mild conditions. The reaction proceeded smoothly under non‐aqueous conditions without the use of any catalyst. Excellent chemoselectivity (i. e., chloroamidation versus dichlorination) could be achieved for electron‐deficient styrenes. In addition, this protocol could be easily applied to 7‐gram‐scale synthesis.

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Ritter-enabled catalytic asymmetric chloroamidation of olefins

Abstract: Intermolecular haloamination reactions are challenging due to the high halenium affinity of the nitrogen atom. This is circumvented by using acetonitrile as an attenuated nucleophile, resulting in an enantioselective halo-Ritter reaction.

Cited by 10 publications

References 103 publications

Structure–Enantioselectivity Relationship (SER) Study of Cinchona Alkaloid Chlorocyclization Catalysts

Structure–Enantioselectivity Relationship (SER) Study of Cinchona Alkaloid Chlorocyclization Catalysts

Exploration of Oxidative Ritter-Type Reaction of α-Arylketones and Its Application for the Collective Total Syntheses of Erythrina Alkaloids

Oxidative Ritter‐type Chloroamidation of Alkenes Using NaCl and Oxone

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